Skip to main content
Top
Published in: BMC Ophthalmology 1/2020

Open Access 01-12-2020 | Angiography | Research article

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography

Authors: Ziyi Zhu, Youling Liang, Bin Yan, Zhishang Meng, Kejun Long, Yiwei Zhang, Jing Luo

Published in: BMC Ophthalmology | Issue 1/2020

Login to get access

Abstract

Background

Varying degrees of macular ischemia generally occur in diabetic retinopathy (DR). This study aims to evaluate the effect of conbercept with 3+ pro re nata (PRN) on macular perfusion status in patients with diabetic macular edema (DME) and quantitatively assess changes in foveal avascular zone (FAZ) areas and capillary density in macular regions by applying optical coherence tomography angiography (OCTA).

Methods

Fifty patients were divided into ischemic (n = 31) and non-ischemic (n = 19) groups according to the presence of ischemia on OCTA at baseline. All patients received intravitreal injections of 0.5 mg of conbercept with 3+ PRN principle. The FAZ areas and macular vessel density measured using OCTA were evaluated at baseline, 3 months, and 6 months after treatment in both groups.

Results

At months 3 and 6, the FAZ area in the ischemic group changed from 0.510 ± 0.171 mm2 to 0.441 ± 0.158 mm2 then to 0.427 ± 0.153 mm2 (p = 0.003, p = 0.296); in the non-ischemic group, it remained stable (p = 0.269, p = 0.926). The superficial vessel density changed from 41.1 ± 4.1 to 42.5% ± 4.7% then to 42.6% ± 4.6% (p = 0.043, p = 0.812), and the deep vessel density changed from 40.7 ± 4.4 to 42.3% ± 3.6% then to 42.3% ± 4.7% (p = 0.072, p = 0.961) in the ischemic group. In the non-ischemic group, the superficial vessel density changed from 44.8 ± 3.2 to 46.0% ± 3.5% then to 45.7% ± 3.3% (p = 0.108, p = 0.666), whereas the deep vessel density changed from 43.6 ± 3.6 to 43.8% ± 3.2% then to 43.5% ± 4.5% (p = 0.882, p = 0.736). Reperfusion in macular nonperfusion areas was observed.

Conclusion

Anti–vascular endothelial growth factor treatment may have a positive effect on macular perfusion status. Furthermore, OCTA had advantages in quantifying and calculating blood flow index in the study of macular perfusion status.
Appendix
Available only for authorised users
Literature
1.
go back to reference Arend O, et al. Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. Br J Ophthalmol. 1991;75(9):514–8..PubMedPubMedCentral Arend O, et al. Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. Br J Ophthalmol. 1991;75(9):514–8..PubMedPubMedCentral
2.
go back to reference Yalcin NG, Ozdek S. The relationship between macular cyst formation and ischemia in diabetic macular edema. Turk J Ophthalmol. 2019;49(4):194–200.PubMedPubMedCentral Yalcin NG, Ozdek S. The relationship between macular cyst formation and ischemia in diabetic macular edema. Turk J Ophthalmol. 2019;49(4):194–200.PubMedPubMedCentral
3.
go back to reference Early Treatment Diabetic Retinopathy Study Research Group. Classification of diabetic retinopathy from fluorescein angiograms: ETDRS report number 11. Ophthalmology. 1991;98(5 Suppl):807–22. Early Treatment Diabetic Retinopathy Study Research Group. Classification of diabetic retinopathy from fluorescein angiograms: ETDRS report number 11. Ophthalmology. 1991;98(5 Suppl):807–22.
4.
5.
go back to reference Li JK, et al. Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab. Int J Ophthalmol. 2015;8(6):1202–6.PubMedPubMedCentral Li JK, et al. Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab. Int J Ophthalmol. 2015;8(6):1202–6.PubMedPubMedCentral
6.
go back to reference Bonini-Filho M, et al. Intravitreal bevacizumab for diabetic macular edema associated with severe capillary loss: one-year results of a pilot study. Am J Ophthalmol. 2009;147(6):1022–30 1030.e1–5.PubMed Bonini-Filho M, et al. Intravitreal bevacizumab for diabetic macular edema associated with severe capillary loss: one-year results of a pilot study. Am J Ophthalmol. 2009;147(6):1022–30 1030.e1–5.PubMed
7.
go back to reference Karst SG, et al. Association of Changes in macular perfusion with Ranibizumab treatment for diabetic macular edema: a subanalysis of the RESTORE (extension) study. JAMA Ophthalmol. 2018;136(4):315–21.PubMedPubMedCentral Karst SG, et al. Association of Changes in macular perfusion with Ranibizumab treatment for diabetic macular edema: a subanalysis of the RESTORE (extension) study. JAMA Ophthalmol. 2018;136(4):315–21.PubMedPubMedCentral
8.
go back to reference Bonnin S, et al. Anti-vascular endothelial growth factor therapy can improve diabetic retinopathy score without change in retinal perfusion. Retina. 2019;39(3):426–34.PubMedPubMedCentral Bonnin S, et al. Anti-vascular endothelial growth factor therapy can improve diabetic retinopathy score without change in retinal perfusion. Retina. 2019;39(3):426–34.PubMedPubMedCentral
9.
go back to reference Couturier A, et al. Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti-vascular endothelial growth factor. Ophthalmology. 2019;126(12):1685–94. Couturier A, et al. Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti-vascular endothelial growth factor. Ophthalmology. 2019;126(12):1685–94.
10.
go back to reference Reddy RK, et al. Efficacy of ranibizumab in eyes with diabetic macular edema and macular nonperfusion in RIDE and RISE. Ophthalmology. 2018;125(10):p1568–74. Reddy RK, et al. Efficacy of ranibizumab in eyes with diabetic macular edema and macular nonperfusion in RIDE and RISE. Ophthalmology. 2018;125(10):p1568–74.
11.
go back to reference Campochiaro PA, et al. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014;121(9):1783–89. Campochiaro PA, et al. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014;121(9):1783–89.
12.
go back to reference Ip MS, et al. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology. 2015;122(2):367–74.PubMed Ip MS, et al. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology. 2015;122(2):367–74.PubMed
13.
go back to reference Ariana L, Irene R, Anton O, et al. Retinal, reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections [J]. Clin Ophthalmol. 2017;11:193–200. Ariana L, Irene R, Anton O, et al. Retinal, reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections [J]. Clin Ophthalmol. 2017;11:193–200.
14.
go back to reference Garcia JM, et al. Diabetic macular ischemia diagnosis: comparison between optical coherence tomography angiography and fluorescein angiography. J Ophthalmol. 2016;2016:3989310.PubMedPubMedCentral Garcia JM, et al. Diabetic macular ischemia diagnosis: comparison between optical coherence tomography angiography and fluorescein angiography. J Ophthalmol. 2016;2016:3989310.PubMedPubMedCentral
15.
go back to reference Jia Y, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20(4):4710–25.PubMedPubMedCentral Jia Y, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20(4):4710–25.PubMedPubMedCentral
16.
go back to reference Cole ED, et al. Contemporary retinal imaging techniques in diabetic retinopathy: a review. Clin Exp Ophthalmol. 2016;44(4):289–99.PubMed Cole ED, et al. Contemporary retinal imaging techniques in diabetic retinopathy: a review. Clin Exp Ophthalmol. 2016;44(4):289–99.PubMed
17.
go back to reference Ren X, et al. Safety and efficacy of intravitreal conbercept injection after vitrectomy for the treatment of proliferative diabetic retinopathy. Eye (Lond). 2019;33(7):1177–83. Ren X, et al. Safety and efficacy of intravitreal conbercept injection after vitrectomy for the treatment of proliferative diabetic retinopathy. Eye (Lond). 2019;33(7):1177–83.
18.
go back to reference Early Treatment Diabetic Retinopathy Study research group. Photocoagulation for diabetic macular edema: ETDRS report number 1. Arch Ophthalmol. 1985;103(12):1796–806. Early Treatment Diabetic Retinopathy Study research group. Photocoagulation for diabetic macular edema: ETDRS report number 1. Arch Ophthalmol. 1985;103(12):1796–806.
19.
go back to reference Larsen M, et al. Individualized Ranibizumab regimen driven by stabilization criteria for central retinal vein occlusion: twelve-month results of the CRYSTAL study. Ophthalmology. 2016;123(5):1101–11.PubMed Larsen M, et al. Individualized Ranibizumab regimen driven by stabilization criteria for central retinal vein occlusion: twelve-month results of the CRYSTAL study. Ophthalmology. 2016;123(5):1101–11.PubMed
20.
go back to reference Camino A, et al. Evaluation of artifact reduction in optical coherence tomography angiography with real-time tracking and motion correction technology. Biomed Opt Express. 2016;7(10):3905–15.PubMedPubMedCentral Camino A, et al. Evaluation of artifact reduction in optical coherence tomography angiography with real-time tracking and motion correction technology. Biomed Opt Express. 2016;7(10):3905–15.PubMedPubMedCentral
21.
go back to reference Hwang TS, Zhang M, Bhavsar K, et al. Visualization of 3 distinct retinal plexuses by projection-resolved optical coherence tomography angiography in diabetic retinopathy. JAMA Ophthalmol. 2016;134(12):1411–9.PubMedPubMedCentral Hwang TS, Zhang M, Bhavsar K, et al. Visualization of 3 distinct retinal plexuses by projection-resolved optical coherence tomography angiography in diabetic retinopathy. JAMA Ophthalmol. 2016;134(12):1411–9.PubMedPubMedCentral
22.
go back to reference Lavia C, et al. Vessel density of superficial, intermediate, and DEEP capillary plexuses using optical coherence tomography angiography. Retina. 2019;39(2):247–58.PubMed Lavia C, et al. Vessel density of superficial, intermediate, and DEEP capillary plexuses using optical coherence tomography angiography. Retina. 2019;39(2):247–58.PubMed
23.
go back to reference Ferris FR, et al. New visual acuity charts for clinical research. Am J Ophthalmol. 1982;94(1):91–6.PubMed Ferris FR, et al. New visual acuity charts for clinical research. Am J Ophthalmol. 1982;94(1):91–6.PubMed
24.
go back to reference Schottenhamml J, et al. An automatic, intercapillary area-based algorithm for quantifying diabetes-related capillary dropout using optical coherence tomography angiography. Retina. 2016;36(Suppl 1):S93–S101.PubMedPubMedCentral Schottenhamml J, et al. An automatic, intercapillary area-based algorithm for quantifying diabetes-related capillary dropout using optical coherence tomography angiography. Retina. 2016;36(Suppl 1):S93–S101.PubMedPubMedCentral
25.
go back to reference Krawitz BD, et al. Parafoveal nonperfusion analysis in diabetic retinopathy using optical coherence tomography angiography. Transl Vis Sci Technol. 2018;7(4):4.PubMedPubMedCentral Krawitz BD, et al. Parafoveal nonperfusion analysis in diabetic retinopathy using optical coherence tomography angiography. Transl Vis Sci Technol. 2018;7(4):4.PubMedPubMedCentral
26.
go back to reference Douvali M, et al. Effect of macular ischemia on intravitreal ranibizumab treatment for diabetic macular edema. Ophthalmologica. 2014;232(3):136–43.PubMed Douvali M, et al. Effect of macular ischemia on intravitreal ranibizumab treatment for diabetic macular edema. Ophthalmologica. 2014;232(3):136–43.PubMed
27.
go back to reference Liu Y, et al. Reversible retinal vessel closure from VEGF-induced leukocyte plugging. JCI Insight. 2017:2(18). Liu Y, et al. Reversible retinal vessel closure from VEGF-induced leukocyte plugging. JCI Insight. 2017:2(18).
28.
go back to reference El DY, et al. Reduced baseline diameter and contraction of peripheral retinal arterioles immediately after remote ischemia in diabetic patients. Graefes Arch Clin Exp Ophthalmol. 2019;257(10):2095–101. El DY, et al. Reduced baseline diameter and contraction of peripheral retinal arterioles immediately after remote ischemia in diabetic patients. Graefes Arch Clin Exp Ophthalmol. 2019;257(10):2095–101.
29.
go back to reference Zhou J, et al. Concentrations of VEGF and PlGF decrease in eyes after Intravitreal Conbercept injection. Diabetes Ther. 2018;9(6):2393–8.PubMedPubMedCentral Zhou J, et al. Concentrations of VEGF and PlGF decrease in eyes after Intravitreal Conbercept injection. Diabetes Ther. 2018;9(6):2393–8.PubMedPubMedCentral
30.
go back to reference Palmhof M, et al. Fewer functional deficits and reduced cell death after Ranibizumab treatment in a retinal ischemia model. Int J Mol Sci. 2018;19(6):1636.PubMedCentral Palmhof M, et al. Fewer functional deficits and reduced cell death after Ranibizumab treatment in a retinal ischemia model. Int J Mol Sci. 2018;19(6):1636.PubMedCentral
31.
go back to reference Inai T, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004;165(1):35–52.PubMedPubMedCentral Inai T, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004;165(1):35–52.PubMedPubMedCentral
32.
go back to reference Dickson PV, et al. Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res. 2007;13(13):3942–50.PubMed Dickson PV, et al. Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res. 2007;13(13):3942–50.PubMed
33.
go back to reference Sim DA, et al. Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography. Am J Ophthalmol. 2014;158(1):144–53 e1.PubMed Sim DA, et al. Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography. Am J Ophthalmol. 2014;158(1):144–53 e1.PubMed
34.
go back to reference Falavarjani KG, et al. Optical coherence tomography angiography analysis of the foveal avascular zone and macular vessel density after anti-VEGF therapy in eyes with diabetic macular edema and retinal vein occlusion. Invest Ophthalmol Vis Sci. 2017;58(1):30–4. Falavarjani KG, et al. Optical coherence tomography angiography analysis of the foveal avascular zone and macular vessel density after anti-VEGF therapy in eyes with diabetic macular edema and retinal vein occlusion. Invest Ophthalmol Vis Sci. 2017;58(1):30–4.
36.
go back to reference Sorour OA, et al. Optical coherence tomography angiography analysis of macular vessel density before and after anti-VEGF therapy in eyes with diabetic retinopathy. Int Ophthalmol. 2019;39(10):2361–71.PubMed Sorour OA, et al. Optical coherence tomography angiography analysis of macular vessel density before and after anti-VEGF therapy in eyes with diabetic retinopathy. Int Ophthalmol. 2019;39(10):2361–71.PubMed
37.
go back to reference Conti FF, et al. Changes in retinal and choriocapillaris density in diabetic patients receiving anti-vascular endothelial growth factor treatment using optical coherence tomography angiography. Int J Retina Vitreous. 2019;5:41.PubMedPubMedCentral Conti FF, et al. Changes in retinal and choriocapillaris density in diabetic patients receiving anti-vascular endothelial growth factor treatment using optical coherence tomography angiography. Int J Retina Vitreous. 2019;5:41.PubMedPubMedCentral
Metadata
Title
Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography
Authors
Ziyi Zhu
Youling Liang
Bin Yan
Zhishang Meng
Kejun Long
Yiwei Zhang
Jing Luo
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2020
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-020-01648-x

Other articles of this Issue 1/2020

BMC Ophthalmology 1/2020 Go to the issue